Abstract

Inversions causing hemophilia A in man will be analyzed by extensive analysis of the three A homologous genes on the X chromosome, one of which lies within the factor VIII gene and gives rise to hemophilia A up to 50% of sporadic cases by intrachromosomal homologous recombination with one of the other two A genes. An animal model of hemophilia A will be produced by homologous recombination in mice. This model will be used to study the potential of somatic cell gene therapy and the development of inhibitory antibodies to factor VIII.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL038165-14
Application #
6017231
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1987-04-01
Project End
2000-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
14
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Genetics
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Leaf, Alexander; Xiao, Yong Fu; Kang, Jing X et al. (2003) Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids. Pharmacol Ther 98:355-77
Fakharzadeh, S S; Zhang, Y; Sarkar, R et al. (2000) Correction of the coagulation defect in hemophilia A mice through factor VIII expression in skin. Blood 95:2799-805
Neerman-Arbez, M; Antonarakis, S E; Honsberger, A et al. (1999) The 11 kb FGA deletion responsible for congenital afibrinogenaemia is mediated by a short direct repeat in the fibrinogen gene cluster. Eur J Hum Genet 7:897-902
Neerman-Arbez, M; Johnson, K M; Morris, M A et al. (1999) Molecular analysis of the ERGIC-53 gene in 35 families with combined factor V-factor VIII deficiency. Blood 93:2253-60
Antonarakis, S E (1998) Molecular genetics of coagulation factor VIII gene and haemophilia A. Haemophilia 4 Suppl 2:1-11
Neerman-Arbez, M; Antonarakis, S E; Blouin, J L et al. (1997) The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103. Am J Hum Genet 61:143-50
Young, M; Inaba, H; Hoyer, L W et al. (1997) Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene. Am J Hum Genet 60:565-73
Bi, L; Sarkar, R; Naas, T et al. (1996) Further characterization of factor VIII-deficient mice created by gene targeting: RNA and protein studies. Blood 88:3446-50
Antonarakis, S E; Kazazian, H H; Gitschier, J et al. (1995) Molecular etiology of factor VIII deficiency in hemophilia A. Adv Exp Med Biol 386:19-34
Antonarakis, S E (1995) Molecular genetics of coagulation factor VIII gene and hemophilia A. Thromb Haemost 74:322-8

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